Increase in microvascular permeability induced by enzymatically generated free radicals. II. Role of superoxide anion radical, hydrogen peroxide, and hydroxyl radical.

The roles played by superoxide anion radical (O,J, hydrogen peroxide, and hydroxyl radical (OH.) in the macromolecular permeability increase seen after addition of xanthine oxidase to the hamster cheek pouch has been studied. Fluorescein-labeled Dextran, l& 150,000 (FITC-Dextran 150) was used to assess microvascular permeability. Application of xanthine oxidase was associated with a marked increase in the observed FITC-Dextran 150 leakage sites per square centimeter. This macromolecular extravasation was significantly reduced by the placement in the reservoir fluid of 50 p&ml superoxide dismutase, an O,scavenger, 50 p,g/ml catalase, and the OH. scavenger dimethyl sulfoxide, and especially by t.-methionine which can react with both OH. and quench singlet 0,. These findings suggest that O,and H20, generated during endogenous substrate-xanthine oxidase reactions result in further generation of OH. which causes the increased macromolecular extravasation possibly mediated through the interactions of OH. with plasmalemmal lipids. A concept of the roles of the individual radical species and their products is presented in the hope that it may aid in the understanding and treatment of inflammatory conditions.